Picture of a microvessel taken with Serial-Block Face Scanning Electron Microscopy on the Electron Microscopy Core Facility in EMBL Heidelberg. The endothelial microvessel is grey with many pericytes sitting on the endothelial floor (totally different colours symbolize particular person pericytes). Credit score: Rory Lengthy/EMBL
Researchers have constructed a 3D human blood-brain barrier within the lab and found a key position of mind pericytes in cerebral malaria illness
Cerebral malaria is a lethal complication of Plasmodium falciparum an infection. Regardless of cutting-edge analysis, efficient anti-malarial medicine, and the promise of a vaccine, it nonetheless claims over half one million lives yearly. Many survivors of cerebral malaria undergo long-term disabilities equivalent to epilepsy, speech problems, or difficulties in motion.
In a brand new examine revealed in EMBO Molecular Medication, researchers at EMBL Barcelona spotlight malaria-induced disruption of pericytes—cells current alongside the partitions of capillaries—bringing us a step nearer to understanding how cerebral malaria damages the mind, and the way these damages might be prevented or reversed.
Cerebral malaria an infection causes extreme injury to the mind’s delicate blood vessels. A central participant on this injury is the angiopoietin-Tie signaling pathway, which usually helps blood vessels keep secure, tight, and guarded.
The conventional functioning of this pathway will depend on the secretion of a molecule referred to as angiopoietin-1 (Ang-1) by pericytes. Sufferers with cerebral malaria typically present an imbalance on this pathway: an excessive amount of of the destabilizing molecule angiopoietin-2 and too little of the protecting Ang-1.
“In this study, we generated an advanced 3D human brain microvasculature model that reproduces important in vivo interactions between human brain endothelial cells and pericytes,” mentioned Rory Lengthy, Postdoctoral Fellow within the Bernabeu Group at EMBL Barcelona and first creator of the work.
“We show that disruption of the crucial role of pericytes in protecting and restoring the blood vessels promotes blood-brain barrier damage during cerebral malaria.”
The crew of researchers constructed a 3D human blood-brain barrier on a chip and recreated key options of the mind’s vascular (blood-vessel-related) setting.
After they uncovered this mannequin to malaria parasite byproducts, Ang-1 secretion was halted, vessels grew to become leaky, and the pericytes themselves confirmed refined injury. When the researchers added again Ang-1, they have been in a position to partially restore vascular stability, highlighting a connection between decreased Ang-1 secretion and blood-brain barrier breakdown.
To deal with the pressing want for novel adjunctive therapies in opposition to cerebral malaria, the authors then examined the therapeutic potential of the angiopoietin-Tie pathway through the use of AKB-9778, a drug that enhances Tie-2 exercise and is at the moment in medical trials for diabetic retinopathy.
They discovered {that a} brief pre-treatment of the 3D blood-brain barrier mannequin with AKB-9778 partially prevented malaria-infected crimson blood cells from disrupting vasculature integrity. Therefore, this examine recognized AKB-9778 and, extra broadly, the restoration of pericyte homeostatic operate as an thrilling new avenue in cerebral malaria remedy.
“Our bioengineered vascular model is a physiologically relevant platform to test additional therapies for cerebral malaria,” mentioned Maria Bernabeu, EMBL Group Chief and senior creator of the publication.
“Experimental rodent studies are not ideal for therapeutic discovery, as malaria affects species differently. Our findings pave the way to identify new therapeutics for cerebral malaria patients.”
Extra data:
Rory Ok M Lengthy et al, Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D mind microvessel mannequin, EMBO Molecular Medication (2025). DOI: 10.1038/s44321-025-00319-y
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European Molecular Biology Laboratory
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The hidden lifetime of pericytes: Understanding how cerebral malaria breaks the blood-brain barrier (2025, October 24)
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